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Green tea polyphenol alleviates silica particle-induced lung injury by suppressing IL-17/NF-κB p65 signaling-driven inflammation 绿茶多酚通过抑制IL-17/NF-κB p65信号驱动的炎症,减轻二氧化硅颗粒诱发的肺损伤。
IF 6.7 1区 医学
Phytomedicine Pub Date : 2024-11-16 DOI: 10.1016/j.phymed.2024.156238
Yunyi Xu , Qionghua Ding , Yuhuan Xie , Qingqing Zhang , Yangyu Zhou , Hairui Sun , Rui Qian , Liqun Wang , Xuxi Chen , Ying Gao , Yuqin Yao , Yue Xiao
{"title":"Green tea polyphenol alleviates silica particle-induced lung injury by suppressing IL-17/NF-κB p65 signaling-driven inflammation","authors":"Yunyi Xu ,&nbsp;Qionghua Ding ,&nbsp;Yuhuan Xie ,&nbsp;Qingqing Zhang ,&nbsp;Yangyu Zhou ,&nbsp;Hairui Sun ,&nbsp;Rui Qian ,&nbsp;Liqun Wang ,&nbsp;Xuxi Chen ,&nbsp;Ying Gao ,&nbsp;Yuqin Yao ,&nbsp;Yue Xiao","doi":"10.1016/j.phymed.2024.156238","DOIUrl":"10.1016/j.phymed.2024.156238","url":null,"abstract":"<div><h3>Background</h3><div>Silicosis, an interstitial lung disease caused by inhalation of silica particles, poses a significant health concern globally. Green tea polyphenol (TP) stands out as a promising therapeutic candidate, yet its specific protective effects and in-depth mechanisms against silicosis have not been thoroughly investigated.</div></div><div><h3>Purpose</h3><div>This study aimed to systematically assess the protective potential of TP against silicosis and to elucidate the underlying mechanisms of its action.</div></div><div><h3>Methods</h3><div>A combination of physiological, transcriptomic, molecular, and computational techniques was employed. HPLC was used to identify the components of TP, and its antioxidant properties were tested with DPPH and ABTS assays. The effects of TP on lung injury were assessed in silicosis mice using histopathology, qRT-PCR, and western blot. Transcriptomic analysis was applied to explore the differentially expressed genes and pathways in response to TP intervention. <em>In vitro</em> studies with mouse alveolar macrophages (MH-S) examined TP's effects on cell viability, proliferation, apoptosis, and inflammation responses. Integrated qRT-PCR, western blot, immunohistochemistry, and molecular docking were performed to confirm the molecular mechanism underlying the protective effects of TP against silicosis.</div></div><div><h3>Results</h3><div>TP effectively attenuated pulmonary inflammation and fibrosis in silicosis mice, as evidenced by significant reductions in inflammation and fibrotic markers. Moreover, TP's therapeutic benefits were linked to its cytoprotective effects on alveolar macrophages, notably its ability to protect MH-S cells from silica particle-induced apoptosis, inhibition of proliferation, and inflammatory response, underscoring its targeted protective effects at the cellular level. Mechanistically, TP exerted its anti-silicosis activity by targeting key pathways implicated in inflammatory responses, notably through the inhibition of the IL-17/NF-κB p65 signaling cascade. Molecular docking simulations corroborated these findings, demonstrating favorable binding affinities between TP's bioactive components (EGC, ECG, and EGCG) and crucial proteins (IL-17A, IL-17F, p65, TNF-α, IL-6, and IL-1β) involved in the IL-17/NF-κB p65 signaling pathway. This pathway inhibition led to a significant decrease in the production of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, thus mitigated silicosis.</div></div><div><h3>Conclusion</h3><div>TP demonstrates efficacy in alleviating silica particle-induced lung injury by suppressing inflammation through the IL-17/NF-κB p65 signaling pathway, underscoring its potential as a valuable natural compound for silicosis management.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156238"},"PeriodicalIF":6.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Jinwu Jiangu capsule attenuates rheumatoid arthritis via the SLC7A11/GSH/GPX4 pathway in M1 macrophages 金乌健骨胶囊通过 M1 巨噬细胞中的 SLC7A11/GSH/GPX4 通路减轻类风湿性关节炎。
IF 6.7 1区 医学
Phytomedicine Pub Date : 2024-11-15 DOI: 10.1016/j.phymed.2024.156232
Yi Ling , Yuzheng Yang , Nina Ren , Hui Xu, Changming Cheng, Daomin Lu, Qiuyi Wang, Xueming Yao, Wukai Ma
{"title":"Jinwu Jiangu capsule attenuates rheumatoid arthritis via the SLC7A11/GSH/GPX4 pathway in M1 macrophages","authors":"Yi Ling ,&nbsp;Yuzheng Yang ,&nbsp;Nina Ren ,&nbsp;Hui Xu,&nbsp;Changming Cheng,&nbsp;Daomin Lu,&nbsp;Qiuyi Wang,&nbsp;Xueming Yao,&nbsp;Wukai Ma","doi":"10.1016/j.phymed.2024.156232","DOIUrl":"10.1016/j.phymed.2024.156232","url":null,"abstract":"<div><h3>Background</h3><div>JinWu JianGu capsule (JWJGC) is a Chinese herbal medicine that alleviates the clinical manifestations of rheumatoid arthritis (RA). However, the mechanism of action requires further investigation..</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the anti-inflammatory effects of JWJGC on RA via the regulation of reactive oxygen species (ROS) and ferroptosis.</div></div><div><h3>Materials and methods</h3><div>JWJGC was administered to rats with collagen-induced arthritis (CIA) via oral gavage for 28 days. In vitro, M1 macrophages were pre-treated with JWJGC-containing serum. After assessing joint swelling and physiologic, the M1/M2 macrophage ratio was detected in CIA rats. The levels of ROS markers were assessed in the serum and cell supernatants. Liquid chromatography-tandem mass spectrometry analyses were employed to check lipid metabolism, and changes in mitochondrial morphology during ferroptosis were detected by transmission electron microscopy. Western blotting, immunofluorescence, immunohistochemistry, and qRT-PCR were performed to validate these results.</div></div><div><h3>Results</h3><div>JWJGC ameliorated CIA by reducing ROS levels in rats. It also restored the balance of the M1/M2 macrophage ratio and reduced the levels of macrophage-related inflammatory markers. Additionally, JWJGC affected lipid metabolism to alleviate inflammation by downregulating lipids associated with ferroptosis. It attenuated ferroptosis by modulating glutathione (GSH)/ Glutathione peroxidase 4(GPX4) expression in CIA rats. In vitro, JWJGC targeted M1 macrophages via the solute carrier family 7a member 11 (SLC7A11)/GSH/GPX4 signaling pathway.</div></div><div><h3>Conclusions</h3><div>This study showed that JWJGC improved RA, primarily through the integrated regulation of the SLC7A11/GSH/GPX4 pathway in M1 macrophages. These findings provide an innovative therapeutic basis for RA treatment and expanding the clinical applications of JWJGC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156232"},"PeriodicalIF":6.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Huang-Lian-Jie-Du decoction alleviates cognitive impairment in high-fat diet-induced obese mice via Trem2/Dap12/Syk pathway 黄连解毒汤通过Trem2/Dap12/Syk途径缓解高脂饮食诱导的肥胖小鼠的认知障碍
IF 6.7 1区 医学
Phytomedicine Pub Date : 2024-11-12 DOI: 10.1016/j.phymed.2024.156248
Jia-Yi Zheng , Rui-Kang Pang , Jiang-Hong Ye , Shan Su , Jia Shi , Yu-Hui Qiu , Hua-Feng Pan , Ru-Yu Zheng , Xin-Rui Hu , Qi-Wen Deng , Xiao-Xiao Li , Ye-Feng Cai , Shi-Jie Zhang
{"title":"Huang-Lian-Jie-Du decoction alleviates cognitive impairment in high-fat diet-induced obese mice via Trem2/Dap12/Syk pathway","authors":"Jia-Yi Zheng ,&nbsp;Rui-Kang Pang ,&nbsp;Jiang-Hong Ye ,&nbsp;Shan Su ,&nbsp;Jia Shi ,&nbsp;Yu-Hui Qiu ,&nbsp;Hua-Feng Pan ,&nbsp;Ru-Yu Zheng ,&nbsp;Xin-Rui Hu ,&nbsp;Qi-Wen Deng ,&nbsp;Xiao-Xiao Li ,&nbsp;Ye-Feng Cai ,&nbsp;Shi-Jie Zhang","doi":"10.1016/j.phymed.2024.156248","DOIUrl":"10.1016/j.phymed.2024.156248","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Cognitive impairment induced by a high-fat diet (HFD) is common, but its mechanism is largely unknown. Huang-Lian-Jie-Du (HLJD) decoction is a classical and powerful prescription in China. It consists of four medicinal plants and is widely used in traditional Chinese medicines (TCM). Studies have shown that HLJD decoction is effective in treating obesity, depression, and so on. However, the therapeutic mechanism of HLJD is still poorly understood.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;Our study aimed to explore whether inflammatory factors and Trem2/Dap12/Syk pathway are involved in this process and whether HLJD treatment can repair cognitive impairment in HFD-induced obesity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;To obtain the obese mice, male mice were treated with HFD (60 Kcal% fat) for 16 weeks. After an additional eight weeks, HLJD decoction was administered orally at doses of 4 and 8 g/kg daily for eight weeks. The mice were then subjected to four behavior tests. Aβ42, total Tau, inflammatory-related, and microglial dysregulation-related markers expression were measured. Molecular docking analysis was also conducted to predict the interaction of the chemical constituents of HLJD with human TREM2, DAP12, and SYK. HLJD at doses of 12.5, 25, and 50 µg/mL or limonin at concentrations of 12.5, 25, and 50 µM were used to treat BV2 cells for 24 h. CCK8 assay and Trem2, Dap12, Syk, and p-Syk expression were measured.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Our study revealed that cognitive impairment was evident in mice treated with HFD, indicating the impact of obesity on cognitive function. The expression of Aβ42 and total Tau in the hippocampus (HIP) was significantly higher in obese (HFD-V) mice compared to normal control (NC-V) mice. The &lt;em&gt;Il6, Il1b&lt;/em&gt;, and &lt;em&gt;Il10&lt;/em&gt; mRNA expression levels were also markedly increased in the HIP of obese mice. Furthermore, Trem2, Dap12, p-Syk, and Iba1 expression were elevated in the HIP of obese mice. Importantly, HLJD treatment was found to repair cognitive impairment and lower the protein expression of Aβ42, Tau, Trem2, Dap12, p-Syk, and the expression of &lt;em&gt;Il6, Il1b&lt;/em&gt;, and &lt;em&gt;Il10&lt;/em&gt; mRNA in HIP of HFD-V mice. The increased expression of Trem2, Dap12, p-Syk, and Iba1 in HIP after HFD consumption could be reduced after receiving HLJD decoction. The compound Limonin showed a well-predicted binding energy with TREM2, DAP12, and SYK. BV2 cells with HLJD or limonin detected the mRNA expressions of &lt;em&gt;Trem2/Dap12&lt;/em&gt;. HLJD at 25 and 50 µg/mL decreased Trem2, Dap12, and p-Syk protein levels in BV2 cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These results reveal that HLJD treatment could alleviate cognitive impairment in HFD-induced obese mice by controlling the activation of the Trem2/Dap12 pathway and reducing Syk phosphorylation in HIP microglia. HLJD and limonin suppressed Trem2/Dap12/Syk signaling pathway in BV2 cells. HLJD therapy might represent a novel treatment","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156248"},"PeriodicalIF":6.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploration the effective components of Gastrodia elata in improving cerebral ischemia reperfusion injury based on "Spectrum-effect" correlation and zebrafish verification experiment. 基于 "光谱效应 "相关性和斑马鱼验证实验,探索天麻改善脑缺血再灌注损伤的有效成分。
IF 6.7 1区 医学
Phytomedicine Pub Date : 2024-11-10 DOI: 10.1016/j.phymed.2024.156211
Zilu Liu, Mengting Wang, Ximeng Ding, Jing Tian, Dan Sun, Xinrui Gao, Chuanshan Jin, Daiyin Peng, Shuangying Gui, Xiaoli Wang
{"title":"Exploration the effective components of Gastrodia elata in improving cerebral ischemia reperfusion injury based on \"Spectrum-effect\" correlation and zebrafish verification experiment.","authors":"Zilu Liu, Mengting Wang, Ximeng Ding, Jing Tian, Dan Sun, Xinrui Gao, Chuanshan Jin, Daiyin Peng, Shuangying Gui, Xiaoli Wang","doi":"10.1016/j.phymed.2024.156211","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156211","url":null,"abstract":"<p><strong>Background: </strong>Gastrodia elata (GE) has been widely used in clinical practice for many years with the functions of relieving stroke, suppressing liver Yang, dispelling wind and clearing collaterals. Our group's previous experimental studies have proved that GE has therapeutic effect on cerebral ischemia reperfusion injury (CIRI) (Ding et al., 2022). However, the active components of GE in treating CIRI remain unclear and require further research.</p><p><strong>Purpose: </strong>The purpose of this paper was to explore the potential effective components of GE improving CIRI based on the \"Spectrum-effect\" correlation. Zebrafish model was used for verification in vivo experimental.</p><p><strong>Materials and methods: </strong>First, the absorption components and metabolites of GE in rat serum were identified using ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS). Second, pharmacodynamic indexes were determined by ELISA kit method, and the effect-time curve of each pharmacodynamic indexes was established. The potential compounds were screened using the statistical method of grey correlation between pharmacodynamic indicator and component response. Finally, the zebrafish CIRI model was successfully established, and the in vivo effect of the active components of GE was verified intuitively.</p><p><strong>Results: </strong>45 chemical components were detected in GE. A total of 87 active components in serum of GE were identified including 25 prototype components and 62 metabolites. GE can improve CIRI by regulating the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), MDA levels and SOD levels. It was found that p‑hydroxy benzaldehyde (PHB), p-hydroxybenzyl alcohol (PHBA) and gastrodin (GA) of GE were the possibly main active components by grey correlation statistics. The in vivo experiments of zebrafish model showed that PHB, PHBA, and GA have the ability to ameliorate cerebral thrombosis by regulation of oxidative stress and apoptosis.</p><p><strong>Conclusions: </strong>The potential active components of GE on CIRI were initially excavated using UHPLC-Q-TOF-MS/MS, pharmacodynamics, and in vivo experiments of zebrafish model. It makes up for the disadvantages of separate research on chemical components and pharmacodynamics, and reflects the material basis of pharmacodynamics more objectively. It has provided theoretical basis for further quality evaluation and scientific foundation for rational drug using of GE in clinical.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156211"},"PeriodicalIF":6.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ginsenoside compound K alleviates brain aging by inhibiting ferroptosis through modulation of the ASK1-MKK7-JNK signaling pathway. 人参皂苷化合物K通过调节ASK1-MKK7-JNK信号通路抑制铁变态反应,从而缓解大脑衰老。
IF 6.7 1区 医学
Phytomedicine Pub Date : 2024-11-10 DOI: 10.1016/j.phymed.2024.156239
Xiaojun Yan, Xue Bai, Guanghui Sun, Zhiguang Duan, Rongzhan Fu, Wen Zeng, Chenhui Zhu, Daidi Fan
{"title":"Ginsenoside compound K alleviates brain aging by inhibiting ferroptosis through modulation of the ASK1-MKK7-JNK signaling pathway.","authors":"Xiaojun Yan, Xue Bai, Guanghui Sun, Zhiguang Duan, Rongzhan Fu, Wen Zeng, Chenhui Zhu, Daidi Fan","doi":"10.1016/j.phymed.2024.156239","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156239","url":null,"abstract":"<p><strong>Background: </strong>Aging of the brain is a major contributor to the onset and progression of neurodegenerative diseases. Conventional treatments for these diseases are often limited by significant side effects and a lack of efficacy in halting disease progression. Ginsenoside compound K (CK), a bioactive secondary metabolite derived from ginseng, has shown promise because of its potent antioxidant properties.</p><p><strong>Purpose: </strong>This study aimed to elucidate the molecular mechanisms underlying the impact of CK on brain senescence, with a particular focus on its role in modulating oxidative stress and related signaling pathways.</p><p><strong>Methods: </strong>We employed a d-galactose (D-gal)-induced PC-12 senescent cell model and a mouse brain aging model to explore the antioxidant properties of CK in the context of brain aging. The effects of CK on mitochondrial dysfunction associated with brain aging were assessed using immunofluorescence and western blotting techniques. The potential molecular mechanisms by CK influences brain aging were investigated using transcriptomic analysis and western blotting. Additionally, CK's regulatory effect on apoptosis signal-regulating kinase 1 (ASK1) was validated by molecular docking, microscale thermophoresis, and small interfering RNA transfection.</p><p><strong>Results: </strong>Our findings demonstrate that CK effectively alleviates cognitive decline associated with brain aging. CK reduces the number of senescent cells, alleviates neuronal damage, and enhances the activity of key antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Additionally, CK restores mitochondrial function and upregulated the expression of solute carrier family 7 member 11 and glutathione peroxidase 4, thereby inhibiting ferroptosis. Furthermore, CK targets ASK1 and suppresses the hyperphosphorylation of MAPK kinase 7 (MKK7) and c-Jun N-terminal kinase (JNK). This suppression promotes the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2), effectively reducing ferroptosis and oxidative damage linked to brain aging.</p><p><strong>Conclusion: </strong>In summary, our research demonstrates that CK effectively delays brain aging by inhibiting the ASK1-MKK7-JNK signaling pathway, enhancing nuclear Nrf2 expression, and suppressing the ferroptosis response. These findings highlight CK as a promising therapeutic agent for slowing brain aging and alleviating neurodegenerative diseases.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156239"},"PeriodicalIF":6.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gastrodin reduces Aβ brain levels in an Alzheimer's disease mouse model by inhibiting P-glycoprotein ubiquitination 天麻素通过抑制 P-glycoprotein 泛素化降低阿尔茨海默氏症小鼠模型的脑内 Aβ 含量。
IF 6.7 1区 医学
Phytomedicine Pub Date : 2024-11-10 DOI: 10.1016/j.phymed.2024.156229
Chenghao Zhu , Shangtao Wang , Siyu Ma , Shurui Zhang , Yanjun Wang , Baoshan Li , Wei Zhang , Zhirong Sun
{"title":"Gastrodin reduces Aβ brain levels in an Alzheimer's disease mouse model by inhibiting P-glycoprotein ubiquitination","authors":"Chenghao Zhu ,&nbsp;Shangtao Wang ,&nbsp;Siyu Ma ,&nbsp;Shurui Zhang ,&nbsp;Yanjun Wang ,&nbsp;Baoshan Li ,&nbsp;Wei Zhang ,&nbsp;Zhirong Sun","doi":"10.1016/j.phymed.2024.156229","DOIUrl":"10.1016/j.phymed.2024.156229","url":null,"abstract":"<div><h3>Background</h3><div>Studies have demonstrated the potential of gastrodin in the treatment of Alzheimer's disease (AD), however, its mechanism of action remains elusive. Currently, the Amyloid-β (Aβ) cascade hypothesis continues to be the prevailing theory regarding AD etiology. The ubiquitination of P-glycoprotein (P-gp) at the blood-brain barrier (BBB) contributes to the accumulation of Aβ in the brain during AD.</div></div><div><h3>Purpose</h3><div>To investigate the mechanism of gastrodin intervention in AD.</div></div><div><h3>Methods</h3><div>The molecular docking, molecular dynamics simulations, and microscale thermophoresis (MST) were employed to identify the action target of gastrodin. The western blot (WB) was performed to detect the protein expression level, the ubiquitination level of P-gp was determined using co-immunoprecipitation (CO-IP) assay. P-gp transport activity was detected using an NBD-CSA fluorescence assay. Trans-Epithelial Electrical Resistance (TEER) was used to detect cell resistance. Fluorescein-labeled dextran experiments were performed to determine the individual cell permeability. The immunofluorescence (IF) was employed to detect Aβ deposition, the Morris Water Maze test was used to assess behavioral changes in APP/PS1 mice and the levels of Aβ40 and Aβ42 expression were quantified using enzyme-linked immunosorbent assay.</div></div><div><h3>Results</h3><div>The FBXO15 was the target of gastrodin-mediated inhibition of P-gp ubiquitination. Gastrodin increased the P-gp expression, cell resistance, and P-gp transport activity of BEND.3 cells upon treatment with Aβ40 through mechanisms involving the reduction of FBXO15 and P-gp binding and the inhibition of P-gp ubiquitination. And gastrodin could effectively improve memory function and increase number of neurons in APP/PS1 mice, reduce the accumulation of Aβ40 and Aβ42, and enhance P-gp expression in a dose-dependent manner.</div></div><div><h3>Conclusion</h3><div>Aβ40 induces the ubiquitination and proteasomal degradation of BBB P-gp, however, gastrodin inhibits the ubiquitination of P-gp by binding to FBXO15, thereby increasing P-gp protein expression and enhancing its transport function.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156229"},"PeriodicalIF":6.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Broussoflavonol F exhibited anti-proliferative and anti-angiogenesis effects in colon cancer via modulation of the HER2-RAS-MEK-ERK pathway. Broussoflavonol F通过调节HER2-RAS-MEK-ERK通路对结肠癌具有抗增殖和抗血管生成作用。
IF 6.7 1区 医学
Phytomedicine Pub Date : 2024-11-09 DOI: 10.1016/j.phymed.2024.156243
Yiying Zhu, Xiaoli Li, Grace Gar-Lee Yue, Julia Kin-Ming Lee, Si Gao, Mengru Wang, Chun Kwok Wong, Wei-Lie Xiao, Clara Bik-San Lau
{"title":"Broussoflavonol F exhibited anti-proliferative and anti-angiogenesis effects in colon cancer via modulation of the HER2-RAS-MEK-ERK pathway.","authors":"Yiying Zhu, Xiaoli Li, Grace Gar-Lee Yue, Julia Kin-Ming Lee, Si Gao, Mengru Wang, Chun Kwok Wong, Wei-Lie Xiao, Clara Bik-San Lau","doi":"10.1016/j.phymed.2024.156243","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156243","url":null,"abstract":"<p><strong>Background: </strong>A prenylated flavonoid, broussoflavonol F (BFF), was isolated from Macaranga genus with cytotoxicities against various cancer cells, though its underlying mechanisms have not been fully elucidated.</p><p><strong>Hypothesis: </strong>This study aimed to investigate the anti-tumor and anti-angiogenesis activities of BFF and its underlying mechanisms in colon cancer.</p><p><strong>Method: </strong>In the in vitro study, the cytotoxic effects of BFF in human colon cancer HCT-116 and LoVo cells were examined using MTT assay, BrdU assay and colony formation assay. The anti-proliferative effects of BFF in these cells were assessed via cell apoptosis and cell cycle analysis using flow cytometry. The anti-angiogenesis effects of BFF in human endothelial HEMC-1 cells were also detected using scratch wound healing assay and tube formation assay. While the in vivo effects of BFF in colon cancer were further examined in zebrafish embryos and HCT116 tumor-bearing mice. The underlying mechanisms of BFF were predicted using network pharmacology analysis, and Western blotting was performed to validate both in vitro and in vivo results.</p><p><strong>Results: </strong>BFF exhibited cytotoxicities on 5 colon cancer cell lines, as well as anti-proliferative activities via inducing apoptosis and cell cycle arrest at the G0/G1 phase in HCT116 and LoVo cells. BFF at 1.25-5 µM also suppressed cell proliferation in these two colon cancer cell lines by downregulating HER2, RAS, p-BRAF, p-MEK and p-Erk protein expressions. In addition, BFF at 2.5-5 µM could significantly decrease the length of subintestinal vessels of zebrafish embryos through decreasing mRNA expressions of NRP1a, PDGFba, PDGFRb, KDR, FLT1 and VEGRaa. Besides, BFF exhibited anti-angiogenesis activity via inhibiting cell proliferation, motility and tube formation in HMEC-1 cells. Furthermore, intraperitoneal administration of BFF (10 mg/kg) suppressed tumor growth and decreased the expression of tumor proliferation marker Ki-67 and angiogenesis marker CD31 in the tumor tissues in HCT116 tumor-bearing mice. BFF treatment could also significantly decrease expressions of RAS, p-BRAF, p-MEK and p-Erk in the tumor section, which are consistent with the in vitro results.</p><p><strong>Conclusions: </strong>This study revealed the anti-tumor and anti-angiogenesis effects of BFF in colon cancer. This is the first report of the in vitro and in vivo anti-proliferative activity of BFF in colon cancer through regulating the HER2-RAS-MEK-ERK pathway. These findings further support the research development of BFF as an anti-cancer agent in colon cancer.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156243"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Semen Cuscutae-Fructus Lycii attenuates tripterygium glycosides-induced spermatogenesis dysfunction by inhibiting oxidative stress-mediated ferroptosis via the Nrf2/HO-1 pathway 菟丝子-枸杞通过Nrf2/HO-1途径抑制氧化应激介导的铁蛋白沉积,从而减轻三叶皂甙诱导的精子发生功能障碍
IF 6.7 1区 医学
Phytomedicine Pub Date : 2024-11-09 DOI: 10.1016/j.phymed.2024.156221
Yutian Zhu , Jiacheng Zhang , Qiuning Liu , Xiyan Xin , Lei Dong , Bin Wang , Haisong Li , Dong Li , Jingshang Wang , Siqi Guan , Yang Ye
{"title":"Semen Cuscutae-Fructus Lycii attenuates tripterygium glycosides-induced spermatogenesis dysfunction by inhibiting oxidative stress-mediated ferroptosis via the Nrf2/HO-1 pathway","authors":"Yutian Zhu ,&nbsp;Jiacheng Zhang ,&nbsp;Qiuning Liu ,&nbsp;Xiyan Xin ,&nbsp;Lei Dong ,&nbsp;Bin Wang ,&nbsp;Haisong Li ,&nbsp;Dong Li ,&nbsp;Jingshang Wang ,&nbsp;Siqi Guan ,&nbsp;Yang Ye","doi":"10.1016/j.phymed.2024.156221","DOIUrl":"10.1016/j.phymed.2024.156221","url":null,"abstract":"<div><h3>Background</h3><div>Semen Cuscutae and Fructus Lycii (SC-FL) is known for its potential therapeutic effects on spermatogenesis dysfunction. However, the underlying mechanisms of SC-FL in alleviating spermatogenesis dysfunction is still being elucidated.</div></div><div><h3>Purpose</h3><div>This study aimed to explore the effects of SC-FL on spermatogenesis dysfunction and investigate the involved mechanisms, specifically focusing on the modulation of oxidative stress and ferroptosis.</div></div><div><h3>Methods</h3><div>A mouse model of spermatogenesis dysfunction was induced by tripterygium glycosides, followed by treatment with SC-FL. Assessment of testicular spermatogenic function in the mice was performed alongside lipidomics analysis to investigate the metabolic mechanisms of SC-FL. The effects on oxidative stress and ferroptosis-related markers were evaluated, the chemical constituents of SC-FL were identified using liquid chromatography-mass spectrometry, and network pharmacology analysis was carried out. Additionally, an in vitro model of spermatogenesis dysfunction was established using triptolide-induced GC-1 cells, which were treated with Lycium barbarum polysaccharides (LBP) and flavonoids from Semen Cuscutae (FSC) to explore their impact on cell damage, oxidative stress-mediated damage, and ferroptosis.</div></div><div><h3>Results</h3><div>SC-FL improved the mouse model of spermatogenesis dysfunction by inhibiting oxidative stress-mediated ferroptosis. In vitro experiments demonstrated that LBP and FSC relieved GC-1 cell damage, with their mechanisms also associated with the inhibition of oxidative stress-mediated ferroptosis.</div></div><div><h3>Conclusion</h3><div>SC-FL alleviates spermatogenesis dysfunction in animal and cell models, potentially through the modulation of the Nrf2/HO-1 signaling pathway, which consequently inhibits oxidative stress-mediated ferroptosis in spermatogonial cells.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156221"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The inhibition of rutin on Src kinase blocks high glucose-induced EGFR/ERK transactivation in diabetic nephropathy by integrative approach of network pharmacology and experimental verification 通过网络药理学与实验验证相结合的方法,研究芦丁对Src激酶的抑制作用可阻断高糖诱导的糖尿病肾病表皮生长因子受体/ERK转录活化。
IF 6.7 1区 医学
Phytomedicine Pub Date : 2024-11-09 DOI: 10.1016/j.phymed.2024.156220
Liang Wu , Luqian Li , Xue Wang , Haixia Wu , Manman Li , Yuxin Wang , Pei Sheng , Xiaofei An , Ming Yan
{"title":"The inhibition of rutin on Src kinase blocks high glucose-induced EGFR/ERK transactivation in diabetic nephropathy by integrative approach of network pharmacology and experimental verification","authors":"Liang Wu ,&nbsp;Luqian Li ,&nbsp;Xue Wang ,&nbsp;Haixia Wu ,&nbsp;Manman Li ,&nbsp;Yuxin Wang ,&nbsp;Pei Sheng ,&nbsp;Xiaofei An ,&nbsp;Ming Yan","doi":"10.1016/j.phymed.2024.156220","DOIUrl":"10.1016/j.phymed.2024.156220","url":null,"abstract":"<div><h3>Background</h3><div>Although clinical strategies for diabetic nephropathy (DN) therapy include stringent blood pressure control through blockade of the renin-angiotensin system and management of hyperglycemia, the condition is still observed to progress relentlessly.</div></div><div><h3>Purpose</h3><div>To elucidate the protective effects of rutin on podocytes in db/db mice with integrative approach of network pharmacology and experimental verification.</div></div><div><h3>Methods</h3><div>The study employs network pharmacology to identify common targets between rutin and DN, constructs a potential protein-protein interaction (PPI) network, and conducts Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking is utilized to evaluate the interaction between rutin and protein targets. Additionally, experimental validation is performed using db/db mice and human podocyte cell models.</div></div><div><h3>Results</h3><div>Rutin has been found to have a significant renoprotective effect, reducing blood glucose, proteinuria, and improving renal function in db/db mice. Rutin's inhibition of Src kinase reduces the phosphorylation levels of EGFR and ERK, which may mitigate podocyte injury. Additionally, rutin exhibits antioxidant properties, capable of lowering the levels of reactive oxygen species (ROS) in kidney tissue and increasing the activity of antioxidant enzymes like superoxide dismutase (SOD). These effects help protect podocytes from oxidative stress, further supporting the potential application of rutin in the treatment of DN.</div></div><div><h3>Conclusions</h3><div>The inhibition of rutin on Src kinase blocks high glucose-induced EGFR/ERK transactivation and protects podocyte injury in DN, indicating it might serve as a promising therapeutic agent for podocyte-targeted therapies.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156220"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Salidroside facilitates neuroprotective effects in ischemic stroke by promoting axonal sprouting through promoting autophagy. 水杨甙通过促进自噬作用促进轴突萌发,从而在缺血性中风中发挥神经保护作用。
IF 6.7 1区 医学
Phytomedicine Pub Date : 2024-11-09 DOI: 10.1016/j.phymed.2024.156208
Wenfang Lai, Yanfeng He, Binbin Zhou, Qingqing Wu, Huiling Wu, Jingquan Chen, Xuerui Zheng, Ru Jia, Pu Lin, Guizhu Hong, Jianyu Chen
{"title":"Salidroside facilitates neuroprotective effects in ischemic stroke by promoting axonal sprouting through promoting autophagy.","authors":"Wenfang Lai, Yanfeng He, Binbin Zhou, Qingqing Wu, Huiling Wu, Jingquan Chen, Xuerui Zheng, Ru Jia, Pu Lin, Guizhu Hong, Jianyu Chen","doi":"10.1016/j.phymed.2024.156208","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156208","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke is a common cerebrovascular disease characterized by high incidence, disability, mortality, and recurrence. The limitations of current pharmacological treatments, which have primarily single neuroprotective action and a narrow therapeutic time window, lead to unsatisfactory therapeutic efficacy. Activation of autophagy can facilitate neural regeneration.</p><p><strong>Objective: </strong>To clarify whether salidroside can promote axonal sprouting through autophagy resulting in protecting neurons.</p><p><strong>Methods: </strong>In vivo, a Middle Cerebral Artery Occlusion/reperfusion (MCAO/IR) model was used, and in vitro, an Oxygen-Glucose Deprivation/Reoxygenation (OGD/R)-induced primary neuronal cell model was employed to evaluate the neuroprotective effects of salidroside. BDA neurotracer, immunofluorescence, and Western blot (WB) were utilized to determine its impact on axonal sprouting and the levels of related proteins (MAP2, GAP43, and PSD-95). Proteomics, transmission electron microscopy (TEM), and WB were applied to identify the effects on autophagy-related proteins (beclin1, LC3, p62, and LAMP2), autophagosomes and lysosomes. The mechanism of salidroside in promoting axonal sprouting through inducing autophagy was further confirmed by blocking with the autophagy inhibitor 3-MA.</p><p><strong>Results: </strong>Salidroside reduced neurologic deficits and infarct volume induced by MCAO/IR in vivo and protected OGD/R induced primary neuronal cells in vitro. Both in vivo and in vitro, it increased the number and length of axons and upregulated the expression of key axonal proteins (MAP2, GAP43, and PSD-95) and mediated autophagy-related proteins. Mechanistic studies showed that the promoting effects of salidroside on autophagy and axonal sprouting disappeared after the blockade by 3-MA.</p><p><strong>Conclusion: </strong>This study reports for the first time that the neuroprotective effect of salidroside in ischemic stroke can be executed through mediating autophagy-related protein (beclin1, LC3, p62, and LAMP2), resulting in induced axonal sprouting or mature protein (MAP2, GAP43, and PSD-95).</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156208"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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